Institute of Pharmacy and Pharmacology, College of Basic Medical Science, Hengyang Medical College, University of South China, Hengyang, China; Division of Regenerative Medicine, Department of Medicine, University of California, San Diego, San Diego, CA, USA.
Institute of Pharmacy and Pharmacology, College of Basic Medical Science, Hengyang Medical College, University of South China, Hengyang, China.
Life Sci. 2021 Sep 15;281:119763. doi: 10.1016/j.lfs.2021.119763. Epub 2021 Jun 26.
Beclin1(BECN1) is known as an autophagy-related protein and the expression is promoted by apelin in lung adenocarcinoma cells, suggesting that apelin activates autophagy in lung adenocarcinoma. However, the functions of apelin-induced autophagy in lung adenocarcinoma tumorigenesis and deterioration are still unknown. Thus, this study aims to investigate the effects of apelin-induced autophagy on lung adenocarcinoma tumorigenesis and deterioration.
Protein expression of exogenous genes were detected by Western blotting analysis. Lung adenocarcinoma cell migration was assessed with cell migration assays. Autophagy was measured with quantification of GFP-LC3 or RFP-GFP-LC3 puncta using fluorescence microscopy in cells by an observed blinded to experimental condition and by western blot analysis of LC3 and p62 in cell lysates as well as autophagy flux. Immunofluorescence staining was performed in human lung adenocarcinoma A549 cells with p-cofilin antibody. The proteins expression in cancer specimens were examined with immunohistochemistry.
Here, we reveal that apelin induces autophagy activation in lung adenocarcinoma. Apelin/APJ regulates BECN1 transcription via HIF1A. Apelin/APJ-activated autophagy promotes lung adenocarcinoma cell migration. Moreover, treatment with autophagy inhibitors significantly decreases apelin/APJ-induced lung adenocarcinoma cell migration. Evaluation of patient samples of lung adenocarcinoma reveals an association between APJ with BECN1 expression and a poor prognosis.
Our studies demonstrate that apelin-induced autophagy promotes lung adenocarcinoma cell migration which suggests a potential therapeutic target for lung adenocarcinoma.
Beclin1（BECN1）是一种自噬相关蛋白，其在肺腺癌细胞中的表达受apelin 促进，提示apelin 在肺腺癌细胞中激活自噬。然而，apelin 诱导的自噬在肺腺癌细胞发生和恶化中的功能尚不清楚。因此，本研究旨在探讨apelin 诱导的自噬对肺腺癌细胞发生和恶化的影响。
通过 Western blot 分析检测外源性基因的蛋白表达。通过细胞迁移实验评估肺腺癌细胞的迁移。通过荧光显微镜观察 GFP-LC3 或 RFP-GFP-LC3 斑点的定量以及细胞裂解物中 LC3 和 p62 的 Western blot 分析以及自噬流来测量自噬。用人肺腺癌细胞 A549 中的 p-cofilin 抗体进行免疫荧光染色。用免疫组织化学法检测癌组织标本中的蛋白表达。
在这里，我们揭示了 apelin 诱导肺腺癌细胞自噬激活。Apelin/APJ 通过 HIF1A 调节 BECN1 转录。Apelin/APJ 激活的自噬促进肺腺癌细胞迁移。此外，自噬抑制剂的处理显著降低了 apelin/APJ 诱导的肺腺癌细胞迁移。对肺腺癌患者样本的评估表明，APJ 与 BECN1 表达之间存在关联，并且与预后不良相关。
我们的研究表明，apelin 诱导的自噬促进肺腺癌细胞迁移，这提示了肺腺癌的潜在治疗靶点。
